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Elife. 2018 Aug 22;7. pii: e36374. doi: 10.7554/eLife.36374.

MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport.

Author information

1
Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, United States.
2
Department of Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, United States.
3
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.

Abstract

Neuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows that the kinesin-1 interacting domain in MAP7 is required for axon and branch growth but not for branch formation. Also, two unique microtubule binding sites are found in MAP7 that have distinct dissociation kinetics and are both required for branch formation. Furthermore, MAP7 recruits kinesin-1 dynamically to microtubules, leading to alterations in organelle transport behaviors, particularly pause/speed switching. As MAP7 is localized to branch sites, our results suggest a novel mechanism mediated by the dual interactions of MAP7 with microtubules and kinesin-1 in the precise control of microtubule-based transport during axon morphogenesis.

KEYWORDS:

MAP7; axon growth and branching; developmental biology; kinesin-1; microtubule; mitochondrial transport; neuroscience; rat

PMID:
30132755
PMCID:
PMC6133550
DOI:
10.7554/eLife.36374
[Indexed for MEDLINE]
Free PMC Article

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